Inflammation-related genes are associated with epigenetic aging in HIV.
Title | Inflammation-related genes are associated with epigenetic aging in HIV. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Sundermann, EE, Hussain, M, Moore, D, Horvath, S, Lin, DTS, Kobor, MS, Levine, AJ |
Corporate Authors | HNRP Group |
Journal | J Neurovirol |
Volume | 25 |
Issue | 6 |
Pagination | 853-865 |
Date Published | 2019 12 |
ISSN | 1538-2443 |
Keywords | CHARTER, Internal |
Abstract | Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH. |
DOI | 10.1007/s13365-019-00777-4 |
Alternate Journal | J. Neurovirol. |
PubMed ID | 31286441 |
PubMed Central ID | PMC6923602 |
Grant List | R25 MH108389 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States R01 DA030913 / DA / NIDA NIH HHS / United States R01 MH096648 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States N01 MH022005 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States R25 MH081482 / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States T32 DA031098 / DA / NIDA NIH HHS / United States |